Clinical Trials /

A Trial of Boost Vaccinations of Pancreatic Tumor Cell Vaccine

NCT01088789

Description:

The purpose of this study is to evaluate the safety and feasibility of long term boost vaccination of a lethally irradiated, allogenic pancreatic tumor cell vaccine transfected with the granulocyte macrophage colony-stimulating factor (GM-CSF) gene alone or given in combination with either a single intravenous dose or daily metronomic oral doses of cyclophosphamide for the treatment of patients with surgically resected adenocarcinoma of the head, neck, tail or the uncinate process of the pancreas.

Related Conditions:
  • Pancreatic Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Trial of Boost Vaccinations of Pancreatic Tumor Cell Vaccine
  • Official Title: A Safety and Feasibility Trial of Boost Vaccinations of a Lethally Irradiated, Allogeneic Pancreatic Tumor Cell Vaccine Transfected With the GM-CSF Gene

Clinical Trial IDs

  • ORG STUDY ID: J09100
  • SECONDARY ID: NA_00031401
  • NCT ID: NCT01088789

Conditions

  • Pancreatic Cancer

Interventions

DrugSynonymsArms
PANC 10.05 pcDNA-1/GM-Neo and PANC 6.03 pcDNA-1 neo vaccine.CyclophosphamideArm A

Purpose

The purpose of this study is to evaluate the safety and feasibility of long term boost vaccination of a lethally irradiated, allogenic pancreatic tumor cell vaccine transfected with the granulocyte macrophage colony-stimulating factor (GM-CSF) gene alone or given in combination with either a single intravenous dose or daily metronomic oral doses of cyclophosphamide for the treatment of patients with surgically resected adenocarcinoma of the head, neck, tail or the uncinate process of the pancreas.

Detailed Description

      Primary Objective:

      1. To evaluate the safety and feasibility of long term boost vaccinations of a lethally
      irradiated, allogeneic pancreatic tumor cell vaccine transfected with the GM-CSF gene given
      alone or in combination with either a single intravenous dose or daily metronomic oral doses
      of cyclophosphamide for the treatment of patients with surgically resected adenocarcinoma of
      the head, neck, or uncinate process of the pancreas.

      Secondary Objective:

        1. To assess the effect of boost vaccinations and long-term treatment of immune modulating
           doses of cyclophosphamide on the number, repertoire and avidity of peripheral
           mesothelin-specific CD8+ T cells.

        2. To estimate disease-free and overall survival of surgically resected pancreatic
           adenocarcinoma patients treated with vaccine boosts with or without low dose
           cyclophosphamide.

      Eligible subjects will receive by intradermal administration the pancreatic tumor vaccine
      consisting of two irradiated, allogeneic pancreatic tumor cell lines transfected with the
      granulocyte macrophage-colony stimulating factor (GM-CSF) gene with or without low dose
      cyclophosphamide. Study participants will be recruited from our prior three arm neoadjuvant
      vaccination with or without low dose cyclophosphamide trial and vaccine naive patients. The
      vaccination boosts will be offered as a continuation of care.

      Patients from the J0810 study will remain on the same arm as the J0810 study where they have
      received the parental vaccine. The first vaccine boost will be given no sooner than six
      months (+/- 1 month) after the last prime vaccination. The vaccine will be administered for
      all arms once every six months (+/- 1 month) after the previous vaccine until ten years have
      passed, the subject no longer meets the eligibility criteria, no longer wishes to participate
      in the study, or the vaccine supply is exhausted. Arm A participants will receive the
      pancreatic cancer vaccine alone. Arm B participants will be vaccinated and receive a single
      low-dose of cyclophosphamide (200 mg/m2) intravenously one day prior to vaccination.
      Participants in Arm C will receive cyclophosphamide 50 mg once a day starting from 28 days
      prior to day 1 of vaccination till 28 days post vaccination.

      Vaccine naive patients will first receive three prime vaccines each one month apart and each
      in combination with a single low-dose of cyclophosphamide (200 mg/m2)intravenously one day
      prior to vaccination. Then they will receive the boost vaccines as the participant in Arm B
      from the J0810 study.
    

Trial Arms

NameTypeDescriptionInterventions
Arm AOtherVaccine only.
  • PANC 10.05 pcDNA-1/GM-Neo and PANC 6.03 pcDNA-1 neo vaccine.
Arm BOtherArm B receives vaccine as well as a single dose of intravenous cyclophosphamide.
  • PANC 10.05 pcDNA-1/GM-Neo and PANC 6.03 pcDNA-1 neo vaccine.
Arm COtherIn addition to Vaccine Arm C receives a daily dose of metronomic cyclophosphamide orally.
  • PANC 10.05 pcDNA-1/GM-Neo and PANC 6.03 pcDNA-1 neo vaccine.

Eligibility Criteria

        Inclusion Criteria:

          1. Has a history of surgically resected and pathologically proved AJCC stage I or stage
             II adenocarcinoma of the head, neck, or uncinate of the pancreas.

          2. Has been a participant in Hopkins IRB protocol (J0810) application number 00-01-58-58
             entitled, "A randomized three-arm neoadjuvant and adjuvant feasibility and toxicity
             study of a GM-CSF secreting allogeneic pancreatic cancer vaccine administered either
             alone or in combination with either a single intravenous dose or daily metronomic oral
             doses of cyclophosphamide for treatment of patients with surgically resected
             adenocarcinoma of the pancreas"( the J0810 cohort), or have never received any type of
             pancreatic cancer vaccine/immunotherapy, had the Whipple surgery within 18 months and
             completed the planned adjuvant chemotherapy and /or chemoradiation (the vaccine naive
             cohort).

          3. Has provided informed consent.

          4. Has received the last irradiated GM-CSF transfected allogeneic pancreatic cell lines
             Panc 10/05/Panc 6.03 at least six months prior (+/- 1 month).Not applicable to the
             vaccine-naive cohort patients.

          5. Has received the last anti-cancer therapy at least 28 days ago.

          6. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

          7. Has adequate hematologic function.(Hemoglobin ≥ 9 g/dL ANC ≥ 1500/mm3 Platelets ≥
             100,000 K/ mm3).

          8. Has adequate renal function? (Serum creatinine ≤ 2 mg/dL).

          9. Has adequate hepatic function. (Bilirubin ≤ 2.0 mg/dl, unless known Gilbert's
             Syndrome; AST, ALT and amylase ≤ 2x upper limit of normal, Alk Phos ≤ 5x upper limit
             of normal).

         10. Agree to use adequate birth control, if of childbearing potential.

        Exclusion Criteria:

          1. Has radiographic evidence of pancreatic cancer recurrence.

          2. Has any documented history of autoimmune diseases including systemic lupus
             erythematosus, sarcoidosis, rheumatoid arthritis, glomerulonephritis,or vasculitis.

          3. Has any uncontrolled medical problems.

          4. Has had systemic steroid therapy within 28 days before vaccine administration.

          5. Has an anticipated need for systemic steroid therapy within 28 days after vaccine
             administration.

          6. Has any evidence of active infections.

          7. Is pregnant.

          8. Has a history of another cancer (other than pancreatic cancer) or myeloproliferative
             disorders in the past five years except for treated non-melanoma skin cancer,
             superficial bladder cancer, or carcinoma in-situ of the cervix.

          9. Has a history of noncompliance during previous vaccination cycles with study treatment
             and/or monitoring which is concerning for continued noncompliance.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Disease free overall survival.
Time Frame:total of 13 years with 6 months between vaccines.
Safety Issue:
Description:Safety as measured by local and systemic toxicity according to NCI CTCAE v 3.0

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Trial Keywords

  • Adenocarcinoma
  • Cyclophosphamide
  • Immunotherapy
  • Neo-Adjuvant
  • Pancreatic tumor vaccine
  • GM-CSF
  • Randomize

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